Search

Decades of research have revealed numerous risk factors for mental disorders beyond genetics, but their consistency and magnitude remain uncer­tain. We conducted a “meta‐umbrella” systematic synthesis of umbrella reviews, which are systematic reviews of meta‐analyses of individual studies, by searching international databases from inception to January 1, 2021. We included umbrella reviews on non‐purely genetic risk or protective factors for any ICD/DSM mental disorders, applying an established classification of the credibility of the evidence: class I (convincing), class II (highly suggestive), class III (suggestive), class IV (weak). Sensitivity analyses were conducted on prospective studies to test for temporality (reverse causation), TRANSD criteria were applied to test transdiagnosticity of factors, and A Measurement Tool to Assess Systematic Reviews (AMSTAR) was employed to address the quality of meta‐analyses. Fourteen eligible umbrella reviews were retrieved, summarizing 390 meta‐analyses and 1,180 associations between putative risk or protective factors and mental disorders. We included 176 class I to III evidence associations, relating to 142 risk/protective factors. The most robust risk factors (class I or II, from prospective designs) were 21. For dementia, they included type 2 diabetes mellitus (risk ratio, RR from 1.54 to 2.28), depression (RR from 1.65 to 1.99) and low frequency of social contacts (RR=1.57). For opioid use disorders, the most robust risk factor was tobacco smoking (odds ratio, OR=3.07). For non‐organic psychotic disorders, the most robust risk factors were clinical high risk state for psychosis (OR=9.32), cannabis use (OR=3.90), and childhood adversities (OR=2.80). For depressive disorders, they were widowhood (RR=5.59), sexual dysfunction (OR=2.71), three (OR=1.99) or four‐five (OR=2.06) metabolic factors, childhood physical (OR=1.98) and sexual (OR=2.42) abuse, job strain (OR=1.77), obesity (OR=1.35), and sleep disturbances (RR=1.92). For autism spectrum disorder, the most robust risk factor was maternal overweight pre/during pregnancy (RR=1.28). For attention‐deficit/hyperactivity disorder (ADHD), they were maternal pre‐pregnancy obesity (OR=1.63), maternal smoking during pregnancy (OR=1.60), and maternal overweight pre/during pregnancy (OR=1.28). Only one robust protective factor was detected: high physical activity (hazard ratio, HR=0.62) for Alzheimer’s disease. In all, 32.9% of the associations were of high quality, 48.9% of medium quality, and 18.2% of low quality. Transdiagnostic class I‐III risk/protective factors were mostly involved in the early neurodevelopmental period. The evidence‐based atlas of key risk and protective factors identified in this study represents a benchmark for advancing clinical characterization and research, and for expanding early intervention and preventive strategies for mental disorders.

Numerous risk factors for mental disorders have been identified. However, we do not know how many disorders we could prevent and to what extent by modifying these risk factors. This study quantifies the Population Attributable Fraction (PAF) of potentially modifiable risk factors for mental disorders. We conducted a PRISMA 2020-compliant (Protocol: https://osf.io/hk2ag) meta-umbrella systematic review (Web of Science/PubMed/Cochrane Central Register of Reviews/Ovi/PsycINFO, until 05/12/2021) of umbrella reviews reporting associations between potentially modifiable risk factors and ICD/DSM mental disorders, restricted to highly convincing (class I) and convincing (class II) evidence from prospective cohorts. The primary outcome was the global meta-analytical PAF, complemented by sensitivity analyses across different settings, the meta-analytical Generalised Impact Fraction (GIF), and study quality assessment (AMSTAR). Seven umbrella reviews (including 295 meta-analyses and 547 associations) identified 28 class I-II risk associations (23 risk factors; AMSTAR: 45.0% high-, 35.0% medium-, 20.0% low quality). The largest global PAFs not confounded by indication were 37.84% (95% CI = 26.77-48.40%) for childhood adversities and schizophrenia spectrum disorders, 24.76% (95% CI = 13.98-36.49%) for tobacco smoking and opioid use disorders, 17.88% (95% CI = not available) for job strain and depression, 14.60% (95% CI = 9.46-20.52%) for insufficient physical activity and Alzheimers disease, 13.40% (95% CI = 7.75-20.15%) for childhood sexual abuse and depressive disorders, 12.37% (95% CI = 5.37-25.34%) for clinical high-risk state for psychosis and any non-organic psychotic disorders, 10.00% (95% CI = 5.62-15.95%) for three metabolic factors and depression, 9.73% (95% CI = 4.50-17.30%) for cannabis use and schizophrenia spectrum disorders, and 9.30% (95% CI = 7.36-11.38%) for maternal pre-pregnancy obesity and ADHD. The GIFs confirmed the preventive capacity for these factors. Addressing several potentially modifiable risk factors, particularly childhood adversities, can reduce the global population-level incidence of mental disorders. Funding Agencies|Wellcome Trust [ENTER: 215793/Z/19/Z]; Spanish Ministry of Science and Innovation; Instituto de Salud Carlos III [SAM16PE07CP1, PI16/02012, PI19/024]; ERDF Funds from the European Commission, "A way of making Europe", CIBERSAM; Madrid Regional Government, European Union Structural Funds [B2017/BMD-3740 AGES-CM-2]; European Union [FP7-4-HEALTH-2009-2.2.1-2-241909, FP7- HEALTH-2013-2.2.1-2-603196, FP7- HEALTH-2013-2.2.1-2-602478]; European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking [115916, 777394]; Fundacion Alicia Koplowitz; Fundacion Familia Alonso

The purpose of this article is to narratively review the empirical literature on clinicians’ emotional, cognitive, and behavioral responses (i.e., countertransference) to depressive and other symptoms of patients with mood disorders. Therapist subjective responses (countertransference) can negatively affect both diagnostic and therapeutic processes, especially when they are not recognized and managed promptly. However, at the same time, countertransference recognition, processing, and management can help inform the diagnostic process and improve the therapy process and outcome. In the last couple of decades, the number of studies that empirically explore countertransference toward mood disordered patients, as well as its relationship with various characteristics of both patients and treatment, has increased. Current evidence suggests that patients with depression tend to elicit more positive feelings among clinicians than patients with other severe mental disorders such as borderline personality disorder or schizophrenia. Furthermore, it documents the existence of associations between patients’ severity of depressive symptoms and clinicians’ subjective reactions, although the results regarding which specific countertransference patterns are evoked in relation to the different phases of the treatment are not entirely consistent. Lastly, growing evidence suggests the presence of clinicians’ specific emotional reactions towards patients with suicidal ideation and behavior.

The patient’s perception of and reaction to the therapist (i.e., the transference) is theoretically and empirically associated with the psychotherapy process and outcome, regardless of the therapeutic approach. However, there are very few measures of transference, and the existing ones are observer- or clinician-report. The current project sought to develop and validate a short self-report inventory. We wrote a set of 131 items, examined the quality of the new measure using subject matter experts, and then collected validation data from a clinical sample of adult patients in individual therapy (N = 701). We used exploratory factor analyses and graded response model item response theory models to select items, confirmatory factor analyses to show that the factor structure fit the data well, and k-fold cross-validation to verify the robustness of our model. Three factors produced short scales retaining the strongest items. The Relationship In-Session Questionnaire (RISQ) has a two-factor structure, yielding a five-item Negative affect scale and a five-item Positive affect scale. The Assessing Risk of Relationship Rupture (ARRR) scale is made up of five items from the third factor with dichotomized responses; it should be used as a warning sign for ruptures in the patient-therapist relationship. Both scales showed excellent psychometric properties. Overall, this study provides an initial validation of both the RISQ and the ARRR scale that can be used in clinical or research settings, with particular value for capturing the patient’s perspectives about their therapist and session-level emotional processes.

Several meta-analyses of observational studies have addressed the association between risk and protective factors and cannabis/cocaine/opioid use disorders, but results are conflicting. No umbrella review has ever graded the credibility of this evidence (not significant/weak/suggestive/highly suggestive/convincing). We searched Pubmed-MEDLINE/PsycInfo, last search September 21, 2020. We assessed the quality of meta-analyses with the AMSTAR-2 tool. Out of 3,072 initial references, five were included, providing 19 associations between 12 putative risk/protective factors and cannabis/cocaine/opioid use disorders (cases: 4539; N = 1,118,872,721). While 84 % of the associations were statistically significant, none was convincing. One risk factor (smoking) had highly suggestive evidence for association with nonmedical use of prescription opioid medicines (OR = 3.07, 95 %CI:2.27 to 4.14). Convincing evidence emerged in sensitivity analyses on antisocial behavior and cannabis use disoder (OR 3.34, 95 %CI 2.53-4.41). Remaining associations had weak evidence. The quality of meta-analyses was rated as moderate in two (40 %), low in one (20 %), and critically low in two (40 %). Future research is needed to better profile risk/protective factors for cannabis/cocaine/opioid use disorders disorders informing preventive approaches.

Acute and transient psychotic disorders (ATPDs) include short-lived psychotic episodes with a high probability of developing psychotic recurrences. Clinical care for ATPD is currently limited by the inability to predict outcomes. Real-world electronic health record (EHR)-based retrospective cohort study STROBE/RECORD compliant included all individuals accessing the South London and Maudsley NHS Trust between 2006 and 2017 and receiving a first diagnosis of ATPD (F23, ICD-10). After imputing missing data, stepwise and LASSO Cox regression methods employing a priori predictors (n = 23) were compared to develop and internally validate an individualized risk prediction model to forecast the risk of psychotic recurrences following TRIPOD guidelines. The primary outcome was prognostic accuracy (area under the curve [AUC]). 3018 ATPD individuals were included (average age = 33.75 years, 52.7% females). Over follow-up (average 1042 ± 1011 days, up to 8 years) there were 1160 psychotic recurrences (events). Stepwise (n = 12 predictors) and LASSO (n = 17 predictors) regression methods yielded comparable prognostic accuracy, with an events per variable ratio >100 for both models. Both models showed an internally validated adequate prognostic accuracy from 4 years follow-up (AUC 0.70 for both models) and good calibration. A refined model was adapted in view of the new ICD-11 criteria on 307 subjects with polymorphic ATPD, showing fair prognostic accuracy at 4 years (AUC: stepwise 0.68; LASSO 0.70). This study presents the first clinically based prediction model internally validated to adequately predict long-term psychotic recurrence in individuals with ATPD. The model can be automatable in EHRs, supporting further external validations and refinements to improve its prognostic accuracy.

Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11–34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7–16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9–25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14–29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15–23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17–48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20–41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20–34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20–33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21–46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.

Psychosocial interventions are recommended in schizophrenia and first-episode psychosis/early psychosis (EP). Nevertheless, literature is heterogeneous and often contradictory. We conducted an umbrella review of (network) meta-analyses of randomized controlled trials (RCTs) comparing psychosocial interventions vs treatment as usual (TAU)/active interventions(ACTIVE)/MIXED controls. Primary outcome was total symptoms (TS); secondary outcomes were positive/negative/depressive symptoms (PS/NS/DS), cognition, functioning, relapse, hospitalization, quality of life (QoL), treatment discontinuation. Standardized mean difference (SMD)/odds ratio (OR)/risk ratio (RR) vs TAU/ACTIVE/MIXED were summarized at end-of-treatment (EoT)/follow-up (FU). Quality was rated as high/medium/low (AMSTAR-PLUS). Eighty-three meta-analyses were included (RCTs = 1246; n = 84,925). Against TAU, regarding TS, Early Intervention Services (EIS) were superior EoT/FU in EP (SMD = −0.32/−0.21), cognitive behavioral therapy (CBT) in schizophrenia EoT/FU (SMD = −0.38/−0.19). Regarding secondary outcomes, in EP, EIS were superior for all outcomes EoT except cognition, and at FU for PS/NS/QoL, specific family interventions (FI-s) prevented relapse EoT; in schizophrenia, superiority emerged EoT for CBT for PS/NS/relapse/functioning/QoL; psychoeducation (EDU)/any FI for relapse; cognitive remediation therapy (CRT) for cognition/functioning; and hallucination-focused integrative treatment for PS. Against ACTIVE, in EP, mixed family interventions (FI-m) were superior at FU regarding TS (SMD = −0.61) and for functioning/relapse among secondary outcomes. In schizophrenia, regarding TS, mindfulness and social skills training (SST) were superior EoT, CBT at FU; regarding secondary outcomes superiority emerged at EoT for computerized cognitive drill-and-practice training for PS/DS, CRT for cognition/functioning, EDU for relapse, individual placement and support (IPS) for employment; and at FU CBT for PS/NS. Against MIXED, in schizophrenia, CRT/EDU were superior for TS EoT (d = −0.14/SMD = −0.33), CRT regarding secondary outcomes EoT for DS/social functioning, both EoT/FU for NS/cognition/global functioning; compensatory cognitive interventions for PS/functioning EoT/FU and NS EoT; CBT for PS at FU, and EDU/SST for relapse EoT. In conclusion, mental health services should consider prioritizing EIS/any FI in EP and CBT/CRT/any FI/IPS for schizophrenia, but other interventions may be helpful for specific outcomes.

To provide a review of journal articles discussing clinical cases or vignettes of psychoanalysis or psychoanalytic psychotherapy of patients affected by bipolar disorder (BD).A thorough search of journal articles was performed in five databases to identify studies published from 1990-2021.Twenty-four articles were included in this review, comprising a total of 29 case reports. The most common theoretical approach adopted by the authors was 'object relations.' Two main sets of clinical-theoretical considerations and recommendations emerge: the applicability of analytic treatment to patients with BD-taking into account their analyzability and practical arrangements for conducting therapy-and theoretical speculations on the nature and development of the illness, as well as on the conceptualization of its different phases.Our findings reveal that there is some psychoanalytic literature providing insight into the psychological dynamics and treatment of patients with BD. Elaboration of this literature may help improve our understanding and provide more accurate and comprehensive descriptions of the intrapsychic and interpersonal dynamics of these patients, yielding potentially valuable information for clinical and research purposes, particularly with regard to reducing interpersonal conflict, and increasing insight and engagement with lifestyle changes and other behaviors likely to promote health and stability.

We mapped the evidence on the type and strength of associations between a broad range of mental and physical conditions in children and adolescents, by carrying out an umbrella review, i.e., a quantitative synthesis of previous systematic reviews and meta-analyses. We also assessed to which extent the links between mental and physical conditions vary across disorders or, by contrast, are transdiagnostic. Based on a pre-established protocol, we retained 45 systematic reviews/meta-analyses, encompassing around 12.5 million of participants. In analyses limited to the most rigorous estimates, we found evidence for the following associations: ADHD-asthma, ADHDobesity, and depression-asthma. A transdiagnostic association was confirmed between asthma and anxiety/ASD/depression/bipolar disorder, between obesity and ADHD/ASD/depression, and between dermatitis and ASD/ADHD. We conclude that obesity and allergic conditions are likely to be associated with mental disorders in children and adolescents. Our results can help clinicians explore potential links between mental and physical conditions in children/adolescent and provide a road map for future studies aimed at shading light on the underlying factors. Funding Agencies|Spanish Ministry of Science, Innovation and Universities [CAS19/00249]; Medical Association of Navarre; European Social Fund; Spanish Research Agency [2017-22060]; NIHR Oxford Cognitive Health Clinical Research Facility; NIHR Research Professorship [RP-2017-08-ST2-006]; NIHR Oxford and Thames Valley Applied Research Collaboration; NIHR Oxford Health Biomedical Research Centre [BRC-1215-20005]

There is limited research in adolescents at risk for psychosis. The new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition attenuated psychosis syndrome (DSM-5 APS) criteria have not been validated in this group. We conducted a RECORD-compliant, real-world, prospective, 5-year cohort study addressing clinical profile, transition to psychosis, and prognostic accuracy of DSM-5 APS in help-seeking inpatient/outpatient adolescents accessing Children and Adolescent Neuropsychiatric services at IRCCS Mondino Foundation (Pavia, Lombardy, Italy) between 2012 and 2019. About 243 adolescents (31 early-onset psychosis [EOP]; 110 meeting DSM-5 APS criteria, DSM-5 APS; 102 not meeting psychotic or DSM-5 APS criteria, non-APS) were included. At baseline, DSM-5 APS adolescents (aged 15.4 ± 1.6) had on average 2.3 comorbid disorders (higher than EOP/non-APS, P < .001). DSM-5 APS adolescents had an intermediate psychopathological profile between non-APS/EOP (P < .001) and worsen Clinical Global Impression-Severity than non-APS (P < .001). DSM-5 APS functioning was intermediate between non-APS and EOP. 39.1% of DSM-5 APS were treated with psychotropic drugs (average = 64 days); 53.6% received psychotherapy. Follow-up of DSM-5 APS and non-APS groups lasted 33 and 26 months, respectively (median). The cumulative risk of transition at 1–5 years was 13%, 17%, 24.2%, 26.8%, and 26.8% in the DSM-5 APS group, 0%, 0%, 3.2%, 3.2%, and 3.2% in the non-APS group. The 5-year prognostic accuracy of the DSM-5 APS in adolescent was adequate (area under the curve = 0.77; Harrell’s C = 0.736, 95%CI 0.697–0.775), with high sensitivity (91.3%) and suboptimal specificity (63.2%). The DSM-5 APS diagnosis can be used to detect help-seeking adolescents at risk of psychosis and predict their long-term outcomes. Future research should consolidate these findings.

Much is not known about the efficacy of interventions to prevent poor mental health outcomes in young people by targeting either the general population (universal prevention) or asymptomatic individuals with high risk of developing a mental disorder (selective prevention).We conducted a PRISMA/MOOSE-compliant systematic review and meta-analysis of Web of Science to identify studies comparing post-test efficacy (effect size [ES]; Hedges' g) of universal or selective interventions for poor mental health outcomes versus control groups, in samples with mean age35 years (PROSPERO: CRD42018102143). Measurements included random-effects models, I2 statistics, publication bias, meta-regression, sensitivity analyses, quality assessments, number needed to treat, and population impact number.295 articles (447,206 individuals; mean age = 15.4) appraising 17 poor mental health outcomes were included. Compared to control conditions, universal and selective interventions improved (in descending magnitude order) interpersonal violence, general psychological distress, alcohol use, anxiety features, affective symptoms, other emotional and behavioral problems, consequences of alcohol use, posttraumatic stress disorder features, conduct problems, tobacco use, externalizing behaviors, attention-deficit/hyperactivity disorder features, and cannabis use, but not eating-related problems, impaired functioning, internalizing behavior, or sleep-related problems. Psychoeducation had the highest effect size for ADHD features, affective symptoms, and interpersonal violence. Psychotherapy had the highest effect size for anxiety features.Universal and selective preventive interventions for young individuals are feasible and can improve poor mental health outcomes.

Formal thought disorder is a cardinal feature of psychotic disorders, and is also evident in subtle forms before psychosis onset in individuals at clinical high-risk for psychosis (CHR-P). Assessing speech output or assessing expressive language with speech as the medium at this stage may be particularly useful in predicting later transition to psychosis.Speech samples were acquired through administration of the Thought and Language Index (TLI) in 24 CHR-P participants, 16 people with first-episode psychosis (FEP) and 13 healthy controls. The CHR-P individuals were then followed clinically for a mean of 7 years (s.d. = 1.5) to determine if they transitioned to psychosis. Non-semantic speech graph analysis was used to assess the connectedness of transcribed speech in all groups.Speech was significantly more disconnected in the FEP group than in both healthy controls (p .01) and the CHR-P group (p .05). Results remained significant when IQ was included as a covariate. Significant correlations were found between speech connectedness measures and scores on the TLI, a manual assessment of formal thought disorder. In the CHR-P group, lower scores on two measures of speech connectedness were associated with subsequent transition to psychosis (8 transitions, 16 non-transitions; p .05).These findings support the utility and validity of speech graph analysis methods in characterizing speech connectedness in the early phases of psychosis. This approach has the potential to be developed into an automated, objective and time-efficient way of stratifying individuals at CHR-P according to level of psychosis risk.

Improving outcomes of a First Episode of Psychosis (FEP) relies on the ability to detect most individuals with emerging psychosis and treat them in specialised Early Intervention (EI) services. Efficacy of current detection strategies is undetermined.RECORD-compliant clinical, 6-year, retrospective, transdiagnostic, lifespan-inclusive, Electronic Health Record (EHR) cohort study, representing real-world secondary mental healthcare in South London and Maudsley (SLaM) NHS. All individuals accessing SLaM in the period 2007-2017 and receiving any ICD-10 diagnosis other than persistent psychosis were included. Descriptive statistics, Kaplan-Meier curves, logistic regression, epidemiological incidence of psychosis in the general population were used to address pathways to care and detection power of EI services for FEP.A total of 106,706 individuals underwent the 6-year follow-up: they were mostly single (72.57%) males (50.51%) of white ethnicity (60.01%), aged on average 32.96 years, with an average Health Of the Nation Outcome Scale score of 11.12 and mostly affected with F40-48 Neurotic/stress-related/somatoform disorders (27.46%). Their transdiagnostic risk of developing a FEP cumulated to 0.072 (95%CI 0.067-0.077) at 6 years. Those individuals who developed a FEP (n = 1841) entered healthcare mostly (79.02%) through inpatient mental health services (29.76%), community mental health services (29.54%) or accident and emergency departments (19.50%); at the time of FEP onset, most of them (46.43%) were under the acute care pathway. Individuals contacting accident and emergency departments had an increased risk of FEP (OR 2.301, 95%CI 2.095-2.534, P 0.001). The proportion of SLaM FEP cases that were eligible and under the care of EI services was 0.456 at any time. The epidemiological proportion of FEP cases in the sociodemographically-matched general population that was detected by EI service was 0.373.More than half of individuals who develop a FEP remain undetected by current pathways to care and EI services. Improving detection strategies should become a mainstream area in the future generation of early psychosis research.

The credibility of evidence of various environmental risk factors for alcohol and tobacco use disorders (AUD/TUD) needs to be graded to identify groups to target with selective prevention. A systematic umbrella review was conducted (PubMed/PsycINFO), grading credibility of meta-analyses of prospective/retrospective observational cohort studies assessing risk/protective factors for AUD/TUD, applying established quantitative criteria. Sensitivity analyses were conducted. Quality of eligible meta-analyses was assessed with AMSTAR-2. Out of 8464 unique references, 80 full text articles were scrutinized, and 12 meta-analyses, corresponding to 21 individual estimates of 12 putative risk/protective factors (n = 241,300), were included. In main analyses no association had convincing nor highly suggestive evidence for AUD/TUD. Six associations had suggestive evidence for AUD, two for TUD. Among these, in sensitivity analyses without >1000 cases criterion, convincing evidence emerged for parental alcohol supply, and impulsivity traits in college students for AUD, and attention-deficit/hyperactivity disorder for TUD. Other associations were supported by weak evidence/were not nominally significant. Few risk factors identified at-risk groups where selective preventative strategies could be developed to prevent AUD/TUD.

Background Primary indicated prevention is a key target for reducing the incidence and burden of schizophrenia and related psychotic disorders. An individualised, clinically-based transdiagnostic model for the detection of individuals at risk of psychosis has been developed and validated in two large, urban healthcare providers. We tested its external validity in a geographically and demographically different non-urban population. Method Retrospective EHR cohort study. All individuals accessing secondary healthcare provided by Oxford Health NHS Foundation Trust between 1st January 2011 and 30th November 2019 and receiving a primary index diagnosis of a non-psychotic or non-organic mental disorder were considered eligible. The previously developed model was applied to this database and its external prognostic accuracy was measured with Harrell's C. Findings The study included n = 33,710 eligible individuals, with an average age of 27.7 years (SD = 19.8), mostly white (92.0%) and female (57.3%). The mean follow-up was 1863.9 days (SD = 948.9), with 868 transitions to psychosis and a cumulative incidence of psychosis at 6 years of 2.9% (95%CI: 2.7–3.1). Compared to the urban development database, Oxford Health was characterised by a relevant case mix, lower incidence of psychosis, different distribution of baseline predictors, higher proportion of white females, and a lack of specialised clinical services for at risk individuals. Despite these differences the model retained an adequate prognostic performance (Harrell's C = 0.79, 95%CI: 0.78–0.81), with no major miscalibration. Interpretation The transdiagnostic, individualised, clinically-based risk calculator is transportable outside urban healthcare providers. Further research should test transportability of this risk prediction model in an international setting.

Background Risk estimation models integrated into Electronic Health Records (EHRs) can deliver innovative approaches in psychiatry, but clinicians' endorsement and their real-world usability are unknown. This study aimed to investigate the real-world feasibility of implementing an individualised, transdiagnostic risk calculator to automatically screen EHRs and detect individuals at-risk for psychosis. Methods Feasibility implementation study encompassing an in-vitro phase (March 2018 to May 2018) and in-vivo phase (May 2018 to April 2019). The in-vitro phase addressed implementation barriers and embedded the risk calculator (predictors: age, gender, ethnicity, index cluster diagnosis, age*gender) into the local EHR. The in-vivo phase investigated the real-world feasibility of screening individuals accessing secondary mental healthcare at the South London and Maudsley NHS Trust. The primary outcome was adherence of clinicians to automatic EHR screening, defined by the proportion of clinicians who responded to alerts from the risk calculator, over those contacted. Results In-vitro phase: implementation barriers were identified/overcome with clinician and service user engagement, and the calculator was successfully integrated into the local EHR through the CogStack platform. In-vivo phase: 3722 individuals were automatically screened and 115 were detected. Clinician adherence was 74% without outreach and 85% with outreach. One-third of clinicians responded to the first email (37.1%) or phone calls (33.7%). Among those detected, cumulative risk of developing psychosis was 12% at six-month follow-up. Conclusion This is the first implementation study suggesting that combining precision psychiatry and EHR methods to improve detection of individuals with emerging psychosis is feasible. Future psychiatric implementation research is urgently needed.

© 2020 Elsevier LtdThe patho-etiology of mental disorders with onset in childhood or adolescence remains largely unknown. We conducted an umbrella review of meta-analyses (MAs) on environmental factors associated with mental disorders with onset in childhood/adolescence. We searched Pubmed-MEDLINE/EMBASE/PsycInfo databases, last search April 29th, 2020. Quality of MAs was measured with AMSTAR-2. Out of 6851 initial references, ten articles met inclusion criteria, providing 23 associations between 12 potential environmental factors and nine disorders (cases: 8884; N = 3,660,670). While almost half of the associations were nominally significant, none of them met criteria from either convincing or highly suggestive evidence. A single association was supported by suggestive evidence (maternal exposure to lithium or antipsychotics with neuromotor deficits), but it was affected by confounding by indication. Ten more associations had weak evidence, and 12 associations were not statistically significant. Quality of meta-analyses was rated as high in two, moderate in one, low in four, critically low in two, and not pertinent in one (individual participant data). Methodologically-sound research is needed in this field.

Background The Psychosis Polyrisk Score (PPS) is a potential biomarker integrating non-purely genetic risk/protective factors for psychosis that may improve identification of individuals at risk and prediction of their outcomes at the individual subject level. Biomarkers that are easy to administer are direly needed in early psychosis to facilitate clinical implementation. This study digitally implements the PPS and pilots its feasibility of use in the real world. Methods The PPS was implemented digitally and prospectively piloted across individuals referred for a CHR-P assessment (n = 16) and healthy controls (n = 66). Distribution of PPS scores was further simulated in the general population. Results 98.8% of individuals referred for a CHR-P assessment and healthy controls completed the PPS assessment with only one drop-out. 96.3% of participants completed the assessment in under 15 min. Individuals referred for a CHR-P assessment had high PPS scores (mean = 6.2, SD = 7.23) than healthy controls (mean = −1.79, SD = 6.78, p

We aim to assess how functioning, depressive symptoms, and psychotic symptoms are associated with different numbers of Clinical High At-Risk Mental State (CHARMS) categories. In this cross-sectional study, we assessed 62 help-seeking subjects aged 15-24 with a drop in functioning, with Structured Clinical Interview for DSM-5, Social and Occupational Functioning Assessment Scale (SOFAS), Comprehensive Assessment of At-Risk Mental State to define risk for psychosis, Hamilton Depression Rating scale (HAM-D), Positive and Negative Symptoms Scale, 6 items (PANSS-6). CHARMS criteria were assessed via retrospective chart review. Overall, 30.6% did not meet any CHARMS component criteria at baseline (CHARMS-), 27.4%, 33.9% and 8.1% met one, two, and three or more CHARMS groups. Overall, 48.8% met criteria for ultra-high risk for psychosis (17.7% without other CHARMS categories), 25.8% risk of borderline personality disorder (3.2% alone), 35.5% mild depression (8.1% alone), 11.3% risk of bipolar disorder (1.6% alone). SOFAS score and HAM-D score worsened from CHARMS- to three or more CHARMS categories, whilst PANSS-6 score did not. In a multivariate regression only PANSS-6 (beta=-1.105, p0.001) was associated with SOFAS (R

Aims: Source monitoring (SM) is the metacognitive ability to determine the origin of one's experiences. SM is altered in primary psychiatric psychosis, although relationships between SM subtypes, other cognitive domains and symptoms are unclear. Our aims were to synthesize evidence comparing psychosis -with and without hallucinations- and healthy controls classifying SM subtypes by source discrimination (internal/external/reality monitoring) and stimulus modality (visual/auditory/imagined/performed). Methods: This systematic review adopted Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Meta-analyses Of Observational Studies in Epidemiology and Population, Intervention, Comparison and Outcomes guidelines. Core demographical and clinical parameters were extracted. Newcastle-Ottawa Scale was used as quality check. SM differences between (i) psychosis patients versus healthy controls and (ii) patients with versus without hallucinations were investigated via random-effect model meta-analysis. The primary effect size measure was standardized mean difference (SMD) in each SM subtype performance (error or accuracy). Heterogeneity, publication biases and meta-regressions were assessed. Results: Five thousand two hundred and fifty-six records were screened to finally include 44 studies (1566 patients, 1175 controls). Mean Newcastle-Ottawa score was 7.41 out of 9. Few studies measured SM associations with cognition (n = 9) and symptoms (n = 19), with heterogeneous findings. SM performance across all measures was reduced in psychosis versus healthy controls (SMD = 0.458). Internal SM (SMD: errors = 0.513; accuracy = 0.733) and imagined stimuli (SMD: errors = 0.688; accuracy = 0.978) were specifically impaired. Patients with versus without hallucinations showed SM deficits only for externalizing (SMD = 0.410) and imagined/auditory (SMD = 0.498/0.277) errors. Conclusion: The proposed classifications highlight specific SM deficits for internal/imagined stimuli in psychosis, providing evidence-based indications to design and interpret future studies.

Hüfner, Katharina, Fabio Caramazza, Agnieszka E. Stawinoga, Evelyn R. Pircher Nöckler, Paolo Fusar-Poli, Sanjeeb S. Bhandari, Buddha Basnyat, Monika Brodmann Maeder, Giacomo Strapazzon, Iztok Tomazin, Barbara Sperner-Unterweger, and Hermann Brugger. Assessment of psychotic symptoms in individuals exposed to very high or extreme altitude: A field study. High Alt Med Biol. 22:369–378, 2021. Background: Symptoms of psychosis such as hallucinations can occur at high or extreme altitude and have been linked to accidents on the mountain. No data are available on how to assess such symptoms in the field and what their prevalence or predisposing factors might be. Methods: In this field study at Everest Base Camp (5,365 m) in Nepal, 99 participants of organized expeditions underwent 279 assessments: The High Altitude Psychosis Questionnaire (HAPSY-Q), the Prodromal Questionnaire, 16-items (PQ-16), and the Mini International Neuropsychiatric Interview (M.I.N.I., psychosis section) were collected together with further clinical data. Statistical analysis was done for each phase, that is, altitude range of the climb, and overall data. Results: One of 97 climbers fulfilled the M.I.N.I. diagnostic criteria for psychosis during one acclimatization climb. At least one endorsed item on the HAPSY-Q and the PQ-16, indicating the presence of symptoms of psychosis in the absence of a psychotic disorders, were identified in 10/97 (10.3%) and 18/87 (20.7%) participants respectively. The scores of the HAPSY-Q and the PQ-16 were correlated (r = 0.268, p

Background The coronavirus disease 2019 (COVID-19) pandemic has been a global challenge. High mortality rates have been reported in some risk groups, including patients with pre-existing mental disorders. Methods We used electronic health records to retrospectively identify people infected due to COVID-19 (between March 2020 and March 2021) in the three territories of the Basque Country. COVID-19 cases were defined as individuals who had tested positive on a reverse transcription-polymerase chain reaction (PCR) test. Univariate and multivariate logistic regression models and multilevel analyses with generalized estimated equations were used to determine factors associated with COVID-19-related mortality and hospital admission. Results The COVID-19 mortality rate was increased for patients with psychotic disorders [odds ratio (OR) adjusted: 1.45, 95% confidence interval (CI) (1.09–1.94), p = 0.0114] and patients with substance abuse [OR adjusted: 1.88, 95% CI (1.13–3.14, p < 0.0152)]. The mortality rate was lower for patients with affective disorders [OR adjusted: 0.80, 95% CI (0.61–0.99), p = 0.0407]. Hospital admission rates due to COVID-19 were higher in psychosis [OR adjusted: 2.90, 95% CI (2.36–3.56), p < 0.0001] and anxiety disorder groups [OR adjusted: 1.54, 95% CI (1.37–1.72), p < 0.0001]. Among admitted patients, COVID-19 mortality rate was decreased for those with affective disorders rate [OR adjusted: 0.72, 95% CI (0.55–0.95), p = 0.0194]. Conclusions COVID-19-related mortality and hospitalizations rates were higher for patients with a pre-existing psychotic disorder.

Recent years have seen the rapid proliferation of clinical prediction models aiming to support risk stratification and individualized care within psychiatry. Despite growing interest, attempts to synthesize current evidence in the nascent field of precision psychiatry have remained scarce. This systematic review therefore sought to summarize progress towards clinical implementation of prediction modeling for psychiatric outcomes. We searched MEDLINE, PubMed, Embase, and PsychINFO databases from inception to September 30, 2020, for English-language articles that developed and/or validated multivariable models to predict (at an individual level) onset, course, or treatment response for non-organic psychiatric disorders (PROSPERO: CRD42020216530). Individual prediction models were evaluated based on three key criteria: (i) mitigation of bias and overfitting; (ii) generalizability, and (iii) clinical utility. The Prediction model Risk Of Bias ASsessment Tool (PROBAST) was used to formally appraise each study’s risk of bias. 228 studies detailing 308 prediction models were ultimately eligible for inclusion. 94.5% of developed prediction models were deemed to be at high risk of bias, largely due to inadequate or inappropriate analytic decisions. Insufficient internal validation efforts (within the development sample) were also observed, while only one-fifth of models underwent external validation in an independent sample. Finally, our search identified just one published model whose potential utility in clinical practice was formally assessed. Our findings illustrated significant growth in precision psychiatry with promising progress towards real-world application. Nevertheless, these efforts have been inhibited by a preponderance of bias and overfitting, while the generalizability and clinical utility of many published models has yet to be formally established. Through improved methodological rigor during initial development, robust evaluations of reproducibility via independent validation, and evidence-based implementation frameworks, future research has the potential to generate risk prediction tools capable of enhancing clinical decision-making in psychiatric care.

BackgroundThe current conceptualization of schizophrenia as neurodevelopmental disorder should lead to innovative public health policies in terms of a reorganization of the mental health care systems, particularly in the transition from adolescence to adulthood, to reduce personal, familiar, and social costs and burdens. The purpose of the project was to perform a survey among a panel of Italian schizophrenia experts, to share evidence-based information on adolescent schizophrenia and explore the degree of consensus among professionals in the following four macro-areas: early diagnosis; pharmacological treatment; health care system organization and transition process from adolescent to adulthood; and psychosocial interventions.MethodsThe consensus process consisted of a two-step web-based Delphi method, which took place between June and November 2021. The survey was developed by a panel of four psychiatrists and four child neuropsychiatrists, identified as key opinion leaders (KOLs). The KOLs identified 21 statements involving a total of 70 items with a major need of clarification on early-onset schizophrenia (EOS). The survey was distributed to 86 specialists in psychiatry and child neuropsychiatry.ResultsThe results revealed a large agreement among the expert group on all the investigated areas of adolescent schizophrenia patterns of care and management. Consensus was ultimately reached for 67 items of the Delphi survey (95.7%), while negative consensus was reached for 2 items and no consensus was reached for 1 item.ConclusionsOverall, results showed a significant gap between the acquired scientific knowledge and clinical practice. In this scenario, it should be necessary to plan specific initiatives at a multiple level, to edit recommendations on clinical decision-making, as well as to prompt changes at the political and organizational levels, also involving scientific societies, patients, and family associations, to overcome the barriers that delay the implementation process.

The Preferred Reporting Items for Overviews of Reviews (PRIOR) statement provides an evidence-based reporting guideline developed using established, rigorous methods that involved a four-stage process (project launch, evidence reviews, modified Delphi exercise, development of the reporting guideline) and an international stakeholder group representing varied experiences (e.g., authors, peer reviewers, editors, readers) and roles (e.g., patients/public, researchers, statisticians, librarians, healthcare professionals, policymakers).The PRIOR statement includes: a checklist with 27 main items that cover all steps and considerations involved in planning and conducting an overview of reviews of healthcare interventions; an explanation and elaboration document with rationale, essential elements, additional elements, and example for each item; and a flow diagram.The methods and results of the PRIOR guideline development, including the checklist and flow diagram, are reported separately. This document contains the explanation and elaboration for each checklist item.

The publication of systematic reviews has rapidly increased making it challenging to remain apprised of and interpret evidence from their growing number. A newer form of evidence synthesis, overview of reviews, synthesizes evidence from multiple systematic reviews. Authors would benefit from evidence- and consensus-based guidance for the complete and transparent reporting of overviews of reviews; in turn this will improve their reproducibility, trustworthiness, and usefulness for readers and end users (e.g., healthcare providers, healthcare decision-makers, policy-makers, patients/public).The PRIOR statement provides an evidence-based reporting guideline developed using established, rigorous methods that involved a four-stage process (project launch, evidence reviews, modified Delphi exercise, development of the reporting guideline) and an international stakeholder group representing varied experiences (e.g., authors, peer reviewers, editors, readers) and roles (e.g., patients/public, researchers, statisticians, librarians, healthcare professionals, policymakers). The PRIOR statement includes: a checklist with 27 main items that cover all steps and considerations involved in planning and conducting an overview of reviews of healthcare interventions; an explanation and elaboration document with rationale, essential elements, additional elements, and example for each item; and a flow diagram.

SummaryUnder standard care, psychotic disorders can have limited response to treatments, high rates of chronicity and disability, negative impacts on families, and wider social and economic costs. In an effort to improve early detection and care of individuals developing a psychotic illness, early intervention in psychosis services and early detection services have been set up in various countries since the 1980s. In April 2016, NHS England implemented a new ‘access and waiting times’ standard for early intervention in psychosis to extend the prevention of psychosis across England. Unfortunately, early intervention and early detection services are still not uniformly distributed in the UK, leaving gaps in service provision. The aim of this paper is to provide a business case model that can guide clinicians and services looking to set up or expand early detection services in their area. The paper also focuses on some existing models of care within the Pan-London Network for Psychosis Prevention teams.

Alzheimer’s disease (AD) results in progressive cognitive decline owing to the accumulation of amyloid plaques and hyperphosphorylated tau. MicroRNAs (miRNAs) have attracted attention as a putative diagnostic and therapeutic target for neurodegenerative diseases. However, existing meta-analyses on AD and its association with miRNAs have produced inconsistent results. The primary objective of this study is to evaluate the magnitude and consistency of differences in miRNA levels between AD patients, mild cognitive impairment (MCI) patients and healthy controls (HC). Articles investigating miRNA levels in blood, brain tissue, or cerebrospinal fluid (CSF) of AD and MCI patients versus HC were systematically searched in PubMed/Medline from inception to February 16th, 2021. Fixed- and random-effects meta-analyses were complemented with the I2 statistic to measure the heterogeneity, assessment of publication bias, sensitivity subgroup analyses (AD severity, brain region, post-mortem versus ante-mortem specimen for CSF and type of analysis used to quantify miRNA) and functional enrichment pathway analysis. Of the 1512 miRNAs included in 61 articles, 425 meta-analyses were performed on 334 miRNAs. Fifty-six miRNAs were significantly upregulated (n = 40) or downregulated (n = 16) in AD versus HC and all five miRNAs were significantly upregulated in MCI versus HC. Functional enrichment analysis confirmed that pathways related to apoptosis, immune response and inflammation were statistically enriched with upregulated pathways in participants with AD relative to HC. This study confirms that miRNAs’ expression is altered in AD and MCI compared to HC. These findings open new diagnostic and therapeutic perspectives for this disorder.

This cohort study quantifies the proportion of real-world individuals with schizophrenia spectrum disorders who would be ineligible for participation in randomized clinical trials and explores whether clinical outcomes differ between eligible and ineligible individuals., Key Points Question What percentage of patients with schizophrenia in the real world are represented in randomized clinical trials (RCTs) and do their outcomes differ from those not represented in RCTs? Findings In this study of 25 259 real-world individuals with diagnoses of schizophrenia spectrum disorders recorded in national patient registries in Finland and Sweden, about a fifth were represented in RCTs and their outcomes were better than of those individuals with schizophrenia not meeting RCT inclusion criteria. Meaning Future research should consider the heterogeneity of individuals with schizophrenia and the patient groups typically ineligible for participation; RCTs may become more inclusive by representing a broader spectrum of individuals with schizophrenia and by targeting specific currently underrepresented groups., Importance Most evidence about efficacy and safety of antipsychotics in schizophrenia spectrum disorders relies on randomized clinical trials (RCTs). However, owing to their strict eligibility criteria, RCTs represent only a part of the real-world population (ie, unselected patients seen in everyday clinical practice), which may result in an efficacy-effectiveness gap. Objective To quantify the proportion of real-world individuals with schizophrenia spectrum disorders who would be ineligible for participation in RCTs, and to explore whether clinical outcomes differ between eligible and ineligible individuals. Design, Setting, and Participants This study applied eligibility criteria typically used in RCTs for relapse prevention in schizophrenia spectrum disorders to real-world populations. Individuals with diagnoses of schizophrenia spectrum disorders recorded in national patient registries in Finland and Sweden were identified. Individuals who had used antipsychotics continuously for 12 weeks in outpatient care were selected. Individuals were followed up for up to 1 year while they were receiving maintenance treatment with any second-generation antipsychotic (excluding clozapine). Follow-up was censored at treatment discontinuation, initiation of add-on antipsychotics, death, and end of database linkage. Main Outcomes and Measures Proportions of RCT-ineligible individuals with schizophrenia spectrum disorders owing to any and specific RCT exclusion criteria. The risk of hospitalization due to psychosis within 1-year follow-up in ineligible vs eligible persons were compared using hazard ratios (HR) and corresponding 95% CIs. Results The mean (SD) age in the Finnish cohort (n = 17 801) was 47.5 (13.8) years and 8972 (50.4%) were women; the mean (SD) age in the Swedish cohort (n = 7458) was 44.8 (12.5) years and 3344 (44.8%) were women. A total of 20 060 individuals (79%) with schizophrenia spectrum disorders would be ineligible for RCTs (Finnish cohort: 14 221 of 17 801 [79.9%]; Swedish cohort: 5839 of 7458 [78.3%]). Most frequent reasons for ineligibility were serious somatic comorbidities and concomitant antidepressant/mood stabilizer use. Risks of hospitalization due to psychosis was higher among ineligible than eligible individuals (Finnish cohort: 18.4% vs 17.2%; HR, 1.14 [95% CI, 1.04-1.24]; Swedish cohort: 20.1% vs 14.8%; HR, 1.47 [95% CI, 1.28-1.92]). The largest risks of hospitalization due to psychosis were observed in individuals ineligible owing to treatment resistance, tardive dyskinesia, and history of suicide attempts. Finally, with more ineligibility criteria met, larger risks of hospitalization due to psychosis were observed in both countries. Conclusions and Relevance RCTs may represent only about a fifth of real-world individuals with schizophrenia spectrum disorders. Underrepresented (ineligible) patients with schizophrenia spectrum disorders have moderately higher risks of admission due to psychosis while receiving maintenance treatment than RCT-eligible patients. These findings set the stage for future studies targeting real-world populations currently not represented by RCTs.

Background The clinical high-risk state for psychosis (CHR-P) paradigm has facilitated the implementation of psychosis prevention into clinical practice; however, advancements in adolescent CHR-P populations are less established. Methods We performed a PRISMA/MOOSE-compliant systematic review of the Web of Science database, from inception until 7 October 2019, to identify original studies conducted in CHR-P children and adolescents (mean age = 36 months.Interventions: There was not enough evidence to recommend one specific treatment (including cognitive behavioural therapy) over the others (including control conditions) to prevent the transition to psychosis in this population. Randomised controlled trials suggested that family interventions, cognitive remediation and fish oil supplementation may improve cognition, symptoms and functioning. At baseline, 30% of CHR-P adolescents were prescribed antipsychotics and 60% received psychotherapy. Conclusions It is possible to detect and formulate a group-level prognosis in adolescents at risk for psychosis. Future interventional research is required. G.S.d.P. and J.V.S. are supported by the Alicia Koplowitz Foundation. The study has been supported by the Spanish Ministry of Science, Innovation, and Universities, Instituto de Salud Carlos III, European Regional Development Fund 'A way of making Europe,' Centro de Investigacion Biomedica en Red Salud Mental, Madrid Regional Government; and Fundacion Mutua Madrilena. A.C. has received personal fees from Janssen and grant support from the Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness. C.A. has been a consultant to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. C.M. has acted as consultant or participated in DMC for Janssen, Servier, Lundbeck, Nuvelution, Angelini and Otsuka and has received grant support from European Union Funds and Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiviness. C.U.C. has been a consultant and/or adviser to or has received honoraria from: Alkermes, Allergan, Angelini, Boehringer-Ingelheim, Gedeon Richter, Gerson Lehrman Group, Indivior, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Merck, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda and Teva. He has provided expert testimony for Bristol-Myers Squibb, Janssen and Otsuka. He served on a Data Safety Monitoring Board for Boehringer-Ingelheim, Lundbeck, Rovi, Supernus, and Teva. He received royalties from UpToDate and grant support from Janssen and Takeda. He is also a shareholder of LB Pharma. P.F-P. has been a consultant to and received research funds from Lundbeck and received honoraria from Menarini and Angelini

Highlights • This systematic review and meta-analysis has identified the top 10 physical and mental health outcomes in health care workers infected or exposed to coronavirus syndromes (Severe Acute Respiratory Syndrome -SARS-, Middle East Respiratory Syndrome -MERS-, Novel coronavirus -COVID-19-). • The physical and mental health burden associated with SARS/MERS/COVID-19 in health care workers is high. • These findings could inform public health strategies to detect the most frequent physical and mental health outcomes in health care workers, monitor their course and implement preventive/treatment measures to mitigate their effect in this vulnerable population., Background Health care workers (HCW) are at high risk of developing physical/mental health outcomes related to coronavirus syndromes. Nature and frequency of these outcomes are undetermined. Methods PRISMA/MOOSE-compliant (PROSPERO-CRD42020180205) systematic review of Web of Science/grey literature until 15th April 2020, to identify studies reporting physical/mental health outcomes in HCW infected/exposed to Severe Acute Respiratory Syndrome -SARS-, Middle East Respiratory Syndrome -MERS-, Novel coronavirus -COVID-19-. Proportion random effect meta-analyses, I2 statistic, quality assessment and sensitivity analysis. Results 115 articles were included (n=60,458 HCW, age 36.1±7.1, 77.1% female). Physical health outcomes: 75.9% HCW infected by SARS/MERS/COVID-19 reported fever (95%CI=65.9–83.7%, k=12, n=949), 47.9% cough (95%CI=39.2–56.8%, k=14, n=970), 43.6% myalgias (95%CI=31.9–56.0%, k=13, n=898), 42.3% chills (95%CI=20.2–67.9%, k=7, n=716), 41.2% fatigue (95%CI=18.2–68.8%, k=6, n=386), 34.6% headaches (95%CI=23.1–48.2%, k=11, n=893), 31.2% dyspnoea (95%CI=23.2–40.5%, k=12, n=1003), 25.3% sore throat (95%CI=18.8–33.2%, k=8, n=747), 22.2% nausea/vomiting (95%CI=14.9–31.8%, k=6, n=662), 18.8% diarrhoea (95%CI=11.9–28.4%, k=9, n=824). Mental health outcomes: 62.5% HCW exposed to SARS/MERS/COVID-19 reported general health concerns (95%CI=57.0–67,8%, k=2, n=2254), 43.7% fear (95%CI=33.9–54.0%, k=4, n=584), 37.9% insomnia (95%CI=30.9–45.5%, k=6, n=5067), 37.8% psychological distress (95%CI=28.4–48.2%, k=15, n=24,346), 34.4% burnout (95%CI=19.3–53.5%, k=3, n=1337), 29.0% anxiety features (95%CI=14.2–50.3%, k=6, n=9191), 26.3% depressive symptoms (95%CI=12.5–47.1%, k=8, n=9893), 20.7% post-traumatic stress disorder features (95%CI=13.2–31%, k=11, n=3826), 16.1% somatisation (95%CI=0.2–96.0%, k=2, n=2184), 14.0% stigmatisation feelings (95%CI=6.4–28.1%, k=2, n=411). Limitations Limited amount of evidence for some outcomes and suboptimal design in several studies included. Conclusions SARS/MERS/COVID-19 have a substantial impact on the physical and mental health of HCW, which should become a priority for public health strategies.

Aims Around 15% of patients at clinical high risk for psychosis (CHR-P) experience symptomatic remission and functional recovery at follow-up, yet the definition of a good outcome (GO) in this population requires further development. Outcomes are typically designed and rated by clinicians rather than patients, to measure adverse as opposed to GOs. Here we investigate how CHR-P subjects define a GO, with the aim of developing a checklist that could be used to measure GO in this clinical group. Methods A set of GO-focused questions were designed in collaboration with a service-user. CHR-P patients (n = 48) were asked to rate the importance of items that could indicate short-term (1 year) and long-term (5 years) GO. These items were then ranked using the relative importance index (RII). Results Patients rated improvement in subjective wellbeing (RII = 0.829) and non-specific presenting symptoms (RII = 0.817) amongst the factors most important for indicating GO in the short-term, and improved resilience (RII = 0.879) and negative symptoms (RII = 0.858) as key items for indicating long-term GO. Patients regarded building resilience (RII = 0.842) and having support from mental health services (RII = 0.833) as being protective for their mental health. These measures were included in a preliminary 12-item GO checklist (GO-12) for assessing GO in CHR-P subjects. Conclusions Patient-defined measures of GO included items that are not incorporated into conventional measures of outcomes in CHR-P subjects, such as subjective wellbeing and resilience. Integrating patient-defined metrics of GO may improve the assessment of outcomes in the CHR-P population.

BACKGROUND Clinical research into the Clinical High Risk state for Psychosis (CHR-P) has allowed primary indicated prevention in psychiatry to improve outcomes of psychotic disorders. The strategic component of this approach is the implementation of clinical services to detect and take care of CHR-P individuals, which are recommended by several guidelines. The actual level of implementation of CHR-P services worldwide is not completely clear. AIM To assess the global geographical distribution, core characteristics relating to the level of implementation of CHR-P services; to overview of the main barriers that limit their implementation at scale. METHODS CHR-P services worldwide were invited to complete an online survey. The survey addressed the geographical distribution, general implementation characteristics and implementation barriers. RESULTS The survey was completed by 47 CHR-P services offering care to 22 248 CHR-P individuals: Western Europe (51.1%), North America (17.0%), East Asia (17.0%), Australia (6.4%), South America (6.4%) and Africa (2.1%). Their implementation characteristics included heterogeneous clinical settings, assessment instruments and length of care offered. Most CHR-P patients were recruited through mental or physical health services. Preventive interventions included clinical monitoring and crisis management (80.1%), supportive therapy (70.2%) or structured psychotherapy (61.7%), in combination with pharmacological treatment (in 74.5%). Core implementation barriers were staffing and financial constraints, and the recruitment of CHR-P individuals. The dynamic map of CHR-P services has been implemented on the IEPA website: https://iepa.org.au/list-a-service/. CONCLUSIONS Worldwide primary indicated prevention of psychosis in CHR-P individuals is possible, but the implementation of CHR-P services is heterogeneous and constrained by pragmatic challenges.

Promotion of good mental health in young people with and without mental disorders has received little empirical research attention and interventions for improving mental health in young people are not well established. This situation could be explained among other reasons due to the difficulties to define and operationalise what good mental health is. The current manuscript, produced by the European College of Neuropsychopharmacology Thematic Working Group on the Prevention of Mental Disorders and Mental Health Promotion (ECNP TWG PMD-MHP), presents a critical review of the available operationalizations for good mental health. A pragmatic conceptual operationalisation of good mental health is a much-needed step towards more standardised research in this field.Good mental health can be defined as a state of well-being that allows individuals to cope with the normal stresses of life and function productively. Universal and selective interventions are suitable to promote mental health. Core domains that define good mental health encompass: (i) mental health literacy, (ii) attitude towards mental disorders, (iii) self-perceptions and values, (iv) cognitive skills, (v) academic/ occupational performance, (vi) emotions, (vii) behaviours, (viii) self-management strategies, (ix) social skills, (x) family and significant relationships (xi) physical health, (xii) sexual health, (xiii) meaning of life, (xiv) and quality of life. These domains should be widely traceable in the literature and can be used to conduct further empirical research in the field of good mental health. Such data can lead to more robust evidence to identify and establish the pathways to follow in order to improve mental health. (C) 2020 The Authors. Published by Elsevier B.V.

Aims The clinical outcomes of individuals at clinical high risk of psychosis (CHR-P) who do not transition to psychosis are heterogeneous and inconsistently reported. We aimed to comprehensively evaluate longitudinally a wide range of outcomes in CHR-P individuals not developing psychosis. Methods “Preferred Reporting Items for Systematic reviews and Meta-Analyses” and “Meta-analysis Of Observational Studies in Epidemiology”-compliant meta-analysis (PROSPERO: CRD42021229212) searching original CHR-P longitudinal studies in PubMed and Web of Science databases up to 01/11/2021. As primary analysis, we evaluated the following outcomes within CHR-P non-transitioning individuals: (a) change in the severity of attenuated psychotic symptoms (Hedge's g); (b) change in the severity of negative psychotic symptoms (Hedge's g); (c) change in the severity of depressive symptoms (Hedge's g); (d) change in the level of functioning (Hedge's g); (e) frequency of remission (at follow-up). As a secondary analysis, we compared these outcomes in those CHR-P individuals who did not transition vs. those who did transition to psychosis at follow-up. We conducted random-effects model meta-analyses, sensitivity analyses, heterogeneity analyses, meta-regressions and publication bias assessment. The risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale (NOS). Results Twenty-eight studies were included (2756 CHR-P individuals, mean age = 20.4, 45.5% females). The mean duration of follow-up of the included studies was of 30.7 months. Primary analysis: attenuated psychotic symptoms [Hedges’ g = 1.410, 95% confidence interval (CI) 1.002–1.818]; negative psychotic symptoms (Hedges’ g = 0.683, 95% CI 0.371–0.995); depressive symptoms (Hedges’ g = 0.844, 95% CI 0.371–1.317); and functioning (Hedges’ g = 0.776, 95% CI 0.463–1.089) improved in CHR-P non-transitioning individuals; 48.7% remitted at follow-up (95% CI 39.3–58.2%). Secondary analysis: attenuated psychotic symptoms (Hedges’ g = 0.706, 95% CI 0.091–1.322) and functioning (Hedges’ g = 0.623, 95% CI 0.375–0.871) improved in CHR-P individuals not-transitioning compared to those transitioning to psychosis, but there were no differences in negative or depressive symptoms or frequency of remission (p > 0.05). Older age was associated with higher improvements of attenuated psychotic symptoms (β = 0.225, p = 0.012); publication years were associated with a higher improvement of functioning (β = −0.124, p = 0.0026); a lower proportion of Brief Limited Intermittent Psychotic Symptoms was associated with higher frequencies of remission (β = −0.054, p = 0.0085). There was no metaregression impact for study continent, the psychometric instrument used, the quality of the study or proportion of females. The NOS scores were 4.4 ± 0.9, ranging from 3 to 6, revealing the moderate quality of the included studies. Conclusions Clinical outcomes improve in CHR-P individuals not transitioning to psychosis but only less than half remit over time. Sustained clinical attention should be provided in the longer term to monitor these outcomes.

State-dependent reallocation of cognitive resources is impaired in schizophrenia and may be underlined by alterations in brain local-connectivity. Increasing evidence suggests local connectivity reductions from rest to task in healthy individuals, while insufficient information is available for schizophrenia spectrum. Resting-state and stop-signal task fMRI scans of 107 healthy controls and 32 patients with DSM-IV-TR schizophrenia or schizoaffective disorder were analyzed. As primary aim we measured within-group shifts in local-connectivity from rest to task as voxel-wise Regional Homogeneity (ReHo-shift). Secondary aims were to test: i) Between-groups differences in ReHo-rest, ReHo-task and ReHo-shift; ii) ReHo covariations with task performance (=shorter reaction times) and severity of symptoms (SAPS/SANS scores). Age, sex, and education were accounted for as covariates. Motion, global-signal-regression, antipsychotic dosage and smoothing associations with ReHo were evaluated. Rest-to-task ReHo reductions occurred in both groups on a whole-brain level (False-Discovery-Rate p=0.05). Trends of greater ReHo reductions in patients versus controls were observed. Controls performed better than patients (p0.001). ReHo negatively correlated with performance in both groups. ReHo-shift predicted worse performance in controls, but better performance in patients (uncorrected p=0.05). ReHo reductions correlated with severity of symptoms. State-dependent reconfigurations in local-connectivity provide new links between neurobiology and behavioral/clinical features of the schizophrenia spectrum.

Psychosis is the most ineffable experience of mental disorder. We provide here the first co‐written bottom‐up review of the lived experience of psychosis, whereby experts by experience primarily selected the subjective themes, that were subsequently enriched by phenomenologically‐informed perspectives. First‐person accounts within and outside the medical field were screened and discussed in collaborative workshops involving numerous individuals with lived experience of psychosis as well as family members and carers, representing a global network of organizations. The material was complemented by semantic analyses and shared across all collaborators in a cloud‐based system. The early phases of psychosis (i.e., premorbid and prodromal stages) were found to be characterized by core existential themes including loss of common sense, perplexity and lack of immersion in the world with compromised vital contact with reality, heightened salience and a feeling that something important is about to happen, perturbation of the sense of self, and need to hide the tumultuous inner experiences. The first episode stage was found to be denoted by some transitory relief associated with the onset of delusions, intense self‐referentiality and permeated self‐world boundaries, tumultuous internal noise, and dissolution of the sense of self with social withdrawal. Core lived experiences of the later stages (i.e., relapsing and chronic) involved grieving personal losses, feeling split, and struggling to accept the constant inner chaos, the new self, the diagnosis and an uncertain future. The experience of receiving psychiatric treatments, such as inpatient and outpatient care, social interventions, psychological treatments and medications, included both positive and negative aspects, and was determined by the hope of achieving recovery, understood as an enduring journey of reconstructing the sense of personhood and re‐establishing the lost bonds with others towards meaningful goals. These findings can inform clinical practice, research and education. Psychosis is one of the most painful and upsetting existential experiences, so dizzyingly alien to our usual patterns of life and so unspeakably enigmatic and human.

Hüfner, Katharina, Fabio Caramazza, Evelyn R. Pircher Nöckler, Agnieszka E. Stawinoga, Paolo Fusar-Poli, Sanjeeb S. Bhandari, Buddha Basnyat, Monika Brodmann Maeder, Giacomo Strapazzon, Iztok Tomazin, Ken Zafren, Hermann Brugger, and Barbara Sperner-Unterweger. Association of pre-existing mental health conditions with acute mountain sickness at Everest Base Camp.

Precision psychiatry is an emerging field with transformative opportunities for mental health. However, the use of clinical prediction models carries unprecedented ethical challenges, which must be addressed before accessing the potential benefits of precision psychiatry. This critical review covers multidisciplinary areas, including psychiatry, ethics, statistics and machine-learning, healthcare and academia, as well as input from people with lived experience of mental disorders, their family, and carers. We aimed to identify core ethical considerations for precision psychiatry and mitigate concerns by designing a roadmap for research and clinical practice. We identified priorities: learning from somatic medicine; identifying precision psychiatry use cases; enhancing transparency and generalizability; fostering implementation; promoting mental health literacy; communicating risk estimates; data protection and privacy; and fostering the equitable distribution of mental health care. We hope this blueprint will advance research and practice and enable people with mental health problems to benefit from precision psychiatry.

OBJECTIVE: People with mood disorders have increased risk of comorbid medical diseases versus the general population. It is paramount to identify interventions to improve physical health in this population.METHODS: Umbrella review of meta-analyses of randomised controlled trials (RCTs) on pharmacological/non-pharmacological interventions for physical health outcomes/intolerability-related discontinuation in mood disorders (any age).RESULTS: Ninety-seven meta-analyses were included. Among youths, against placebo, in depression, antidepressants/antipsychotics had higher discontinuation rates; in bipolar depression, olanzapine+fluoxetine worsened total cholesterol (TC)/triglycerides/weight gain (WG) (large ES). In adults with bipolar disorder, olanzapine worsened HbA1c/TC/WG (moderate/large ES); asenapine increased fasting glucose (small ES); quetiapine/cariprazine/risperidone induced WG (small/moderate ES). In bipolar depression, lurasidone was metabolically neutral. In depression, psychological interventions improved physical health-related quality of life (PHQoL) (small ES), fasting glucose/HbA1c (medium/large ES); SSRIs improved fasting glucose/HbA1c, readmission for coronary disease, pain (small ES); quetiapine/aripiprazole/olanzapine induced WG (small to large ES). Exercise improved cardiorespiratory fitness (moderate ES). In the elderly, fluoxetine yielded more detrimental cardiovascular effects than sertraline/escitalopram (large ES); antidepressants were neutral on exercise tolerance and PHQoL. In mixed age groups, in bipolar disorder aripiprazole was metabolically neutral; in depression, SSRIs lowered blood pressure versus placebo and serotonin-noradrenaline reuptake inhibitors (small ES); brexpiprazole augmentation caused WG and was less tolerated (small ES); exercise improved PHQoL (moderate ES).CONCLUSIONS: Some interventions (psychological therapies, exercise and SSRIs) improve certain physical health outcomes in mood disorders, few are neutral, but various pharmacological interventions are associated with negative effects. Evidence from this umbrella review has limitations, should consider evidence from other disorders and should be integrated with recent evidence from individual RCTs, and observational evidence. Effective treatments with either beneficial or physically neutral profiles should be prioritized.

Christoph U Correll,1– 3 Paolo Fusar-Poli,4– 6 Stefan Leucht,7 Anne Karow,8 Nadja Maric,9 Carmen Moreno,10 Merete Nordentoft,11 Andrea Raballo12,13 1Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany; 2Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; 3Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, NY, USA; 4Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK; 5OASIS service, South London and Maudsley NHS Foundation Trust, London, UK; 6Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy; 7Section Evidence-Based Medicine in Psychiatry and Psychotherapy, Department of Psychiatry and Psychotherapy, Technical University of Munich, School of Medicine, Munich, Germany; 8Department of Psychiatry and Psychotherapy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; 9Faculty of Medicine, University of Belgrade and Institute of Mental Health, Belgrade, Serbia; 10Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain; 11CORE-Copenhagen Research Centre for Mental Health, Mental Health Services in the Capital Region, Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; 12Section of Psychiatry, Clinical Psychology and Rehabilitation, Department of Medicine, University of Perugia, Perugia, Italy; 13Centre for Translational, Phenomenological and Developmental Psychopathology (CTPDP), Perugia University Hospital, Perugia, ItalyCorrespondence: Christoph U CorrellDepartment of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Augustenburger Platz 1, Berlin, 13353, Germany, Tel +49-30-450-566202, Fax +49-30-450-566921, Email christoph.correll@charite.dePurpose: Although first-episode psychosis (FEP) in youth, particularly early-onset schizophrenia (EOS), is managed similarly to adult-onset schizophrenia, few antipsychotics are approved for people aged 13– 18 years. We aimed to explore areas of uncertainty in EOS management and provide evidence-based recommendations to mental health specialists. We used the Delphi methodology to gain knowledge in areas lacking evidence-based strategies. This standardized methodology consists of the development of a questionnaire by content experts, which is then submitted to a broader panel of professionals (panelists) to survey their level of agreement on the topics proposed.Materials and Methods: The developed questionnaire covered patient management from diagnosis to maintenance treatment and was administered to a broader panel of specialists across Europe. Based on an analysis of responses received in this first round, the items that needed further insight were submitted to the panel for a second round and then reanalysed.Results: An initial set of 90 items was developed; in round I, consensus was reached for 83/90 items (92%), while it was reached for 7/11 (64%) of the items sent out for rerating in round II. Feedback for rounds I and II was obtained from 54/92 and 48/54 approached experts, respectively. There was broad agreement on diagnostic standards, multimodal approaches and focus on adverse events, but uncertainty in terms of pharmacological strategies (including clozapine) in case of failure and antipsychotic dosing in younger patients.Conclusion: Despite knowledge about diagnostic clues and integrated management of EOS, this study highlights the lack of standardization in treating EOS, with safety arguments having a major role in the decision-making process. Targeted clinical trials and systematic dissemination across Europe of current scientific evidence on the value of early intervention services is hoped to contribute to standardized and improved quality care for patients with early-phase psychosis and schizophrenia.Keywords: schizophrenia, Delphi, psychosis, early onset, management

IntroductionPeople often experience significant difficulties in receiving mental healthcare due to insufficient resources, stigma and lack of access to care. Remote care technology has the potential to overcome these barriers by reducing travel time and increasing frequency of contact with patients. However, the safe delivery of remote mental healthcare requires evidence on which aspects of care are suitable for remote delivery and which are better served by in-person care. We aim to investigate clinical and demographic associations with remote mental healthcare in a large electronic health record (EHR) dataset and the degree to which remote care is associated with differences in clinical outcomes using natural language processing (NLP) derived EHR data.Methods and analysisDeidentified EHR data, derived from the South London and Maudsley (SLaM) National Health Service Foundation Trust Biomedical Research Centre (BRC) Case Register, will be extracted using the Clinical Record Interactive Search tool for all patients receiving mental healthcare between 1 January 2019 and 31 March 2022. First, data on a retrospective, longitudinal cohort of around 80 000 patients will be analysed using descriptive statistics to investigate clinical and demographic associations with remote mental healthcare and multivariable Cox regression to compare clinical outcomes of remote versus in-person assessments. Second, NLP models that have been previously developed to extract mental health symptom data will be applied to around 5 million documents to analyse the variation in content of remote versus in-person assessments.Ethics and disseminationThe SLaM BRC Case Register and Clinical Record Interactive Search (CRIS) tool have received ethical approval as a deidentified dataset (including NLP-derived data from unstructured free text documents) for secondary mental health research from Oxfordshire REC C (Ref: 18/SC/0372). The study has received approval from the SLaM CRIS Oversight Committee. Study findings will be disseminated through peer-reviewed, open access journal articles and service user and carer advisory groups.